Møiniche et al 2002

A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia.

Møiniche S, Kehlet H, Dahl JB.

Anesthesiology 2002;96(3):725–741.

De Kock et al 1994

Intraoperative and postoperative analgesia using intravenous opioid, clonidine and lignocaine.

De Kock M, Lavandhomme P, Scholtes JL.

Anaesth Intensive Care 1994;22(1):15–21.

The postoperative analgesia afforded after colonic surgery by IV opioid, clonidine and lignocaine given intra- and postoperatively was evaluated. In a double-blind randomised trial, 80 male patients scheduled for colonic resection under general anaesthesia received fentanyl 5 micrograms.kg-1 at induction and another 4 micrograms.kg-1 before skin incision (group A) or fentanyl (same dose) plus clonidine 4 micrograms.kg-1 in 20 min + 2 micrograms.kg-1.h-1 (group B, C) or fentanyl plus clonidine (same dosage) plus lignocaine 2 mg.kg-1 before skin incision, repeated before peritoneal incision and retractor placement (group D). In the four groups, intraoperative boluses of fentanyl 2 micrograms.kg-1 were given in response to the painful stimulation of the procedure. Postoperative pain was managed with PCA delivering 2 mg morphine per request in group A, 1.5 mg morphine in group B, 1.5 mg morphine + 15 micrograms clonidine in group C and 1.2 mg morphine + 15 micrograms clonidine + 23 mg lignocaine in group D. Postoperative analgesia was assessed by recording the analgesic demands (met and unmet) and the dose of morphine delivered at 6, 12, 18, 24, 36 hours. Side-effects, pain and sedation analogue scores were also recorded. Analgesic demands and delivered morphine dose were reduced, at any time interval considered, in groups B, C, D, compared with A (P < 0.001). No differences were noted between the group B, C, D. Pain analogue scores were better in groups B, C, D compared with group A (P < 0.001). Sedation and side-effects were not increased in groups B, C, D.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimou et al 2003

Transdermal clonidine: does it affect pain after abdominal hysterectomy?

Dimou P, Paraskeva A, Papilas K, Fassoulaki A.

Acta Anaesthesiol Belg 2003;54(3):227–232.

Clonidine has analgesic properties. We evaluated the analgesic effect of clonidine perioperatively. Forty patients undergoing abdominal hysterectomy received randomly the evening before surgery transdermal clonidine covered with overlay (CLO group) or the overlay alone (CTL group). Ten min before induction they received i.v. clonidine 1 microgram.kg-1 (CLO) or normal saline (CTL). Induction was accomplished with fentanyl 5 micrograms.kg-1, thiopentone 5 mg.kg-1, cis-atracurium 0.15 mg.kg-1 and maintenance with sevoflurane 2% in 70% N2O. Hemodynamic parameters were recorded intraoperatively. Pain was assessed by VAS at rest and movement 2, 4, 6, 8, 24, 48, 72 h and 30 days, postoperatively. During the first 8 h postoperatively all patients received controlled analgesia with fentanyl followed by morphine i.m. 0.15 mg.kg-1 and paracetamol. From 24-72 h postoperatively, patients received 75 mg propoxyphene and 600 mg paracetamol i.m., on demand. Arterial blood pressure was lower in the CLO group 0, 3, 10 min after intubation. There was no difference in pain or fentanyl consumption 8 h postoperatively. The CLO group required less analgesics 24 h postoperatively (p = 0.023). The two groups did not differ in pain or analgesic requirements 72 h and 30 days postoperatively. Clonidine had a weak opioid sparing effect 24 h post-operatively, but did not affect pain in long term.

Owen et al 1997

STUDY OBJECTIVE: To determine if a lower than previously reported oral-transdermal clonidine regimen could reduce postoperative morphine requirements without producing systemic side effects. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: University-affiliated hospital. PATIENTS: 29 healthy, ASA physical status I and II females undergoing elective abdominal hysterectomy. INTERVENTIONS: Patients received preoperative oral clonidine 4 to 5 mu/kg and a 7 cm2 transdermal clonidine patch (0.2 mg/24 hours) or a placebo tablet and patch. MEASUREMENTS AND MAIN RESULTS: Postoperative patient-controlled analgesia pumps provided morphine during the 48-hour study period. Morphine use, hemodynamic changes, and nonhemodynamic side effects were recorded. Additionally, visual analog pain scales (VAPS) and plasma concentrations of morphine and clonidine were measured. We found that low-dose clonidine had no potentiating effect on morphine analgesia. Postoperative morphine use, VAPS, and morphine plasma levels were similar between the control and clonidine-treated groups. Nevertheless, patients in the clonidine group experienced a significantly greater incidence of intraoperative and postoperative hypotension and bradycardia than did the control group. No differences were noted in the incidence of nonhemodynamic side effects. CONCLUSIONS: The low-dose oral-transdermal clonidine regimen evaluated failed to reduce postoperative morphine requirements, although patients who received clonidine were still at risk for developing hypotension.

Lee et al 2008

Timing of intraoperative parecoxib analgesia in colorectal surgery

Lee LH, Irwin MG, Yao TJ, Yuen MK, Cheung CW.

Acute Pain 2008;10(3-4):123-130.

Objective: The aim of this study was to determine the analgesic effect of parecoxib when administered either before or at the end of surgery in patients undergoing colorectal laparotomy.

Methods: Sixty patients were randomised to three groups of 20. The PS group received intravenous parecoxib 40mg before skin incision and normal saline at skin closure. The SP group received saline before skin incision and intravenous parecoxib 40mg at skin closure. A control group (SS) received saline at both time points.

Results: In both SP and PS groups, morphine consumption was smaller. There was a 40–55% reduction in cumulative morphine consumption in both treatment groups at all time points up to 48h after anaesthesia finished. The greatest reduction was from 12h to 24h which showed a 66% reduction for the SP group and a 55% reduction for the PS group compared to control (p=0.0003 and 0.0049, respectively, with an adjusted significance value=0.0167). For SP and PS groups, the time to first post-operative analgesic request tended to be longer and the number of patients requesting morphine in the recovery room was less.

Conclusion: Parecoxib administration at the end of surgery is as effective as at the beginning with regard to analgesic and opioid-sparing effects.

Sim et al 2007

Prospective randomized, double-blind, placebo-controlled study of pre- and postoperative administration of a COX-2-specific inhibitor as opioid-sparing analgesia in major colorectal surgery.

Sim R, Cheong DM, Wong KS, Lee BM, Liew QY.

Colorectal Dis 2007;9(1):52-60.

PURPOSE: To demonstrate the opioid-sparing effect and reduction in postoperative ileus obtained with valdecoxib 40 mg administered pre- and postoperatively in patients undergoing colorectal resection. METHODS: Patients for elective colorectal resection from December 2002 to June 2004 were randomized to receive either valdecoxib or placebo with standard patient-controlled analgesia (PCA) morphine. In the study arm, the first dose of valdecoxib 40 mg was administered orally as close as possible to 1 h prior to the start of surgery. Each subsequent dose was administered at 24-h intervals up to 120 h. Patients in the control arm were served placebos at the same time-points. RESULTS: Forty patients were enrolled in the study arm and 39 (excluding one protocol violation) in the control arm. The groups were comparable in age, sex, American Society of Anesthesiology status, body mass index, incision length, and duration and types of operations. Mean PCA doses at 12 and 24 h were 18.6 and 28.3 mg in the study arm vs 26.2 and 41.2 mg in controls, representing a one-third opioid reduction. Bowel sound and movement first appeared at medians of 12 and 72 h in the study arm vs 24 and 84 h, respectively, in controls (P < 0.05). Tolerance of solid diet was at a median of 60 h and discharge at a median of 4 days in the study arm vs 72 h and 6 days in controls (P < 0.05 and P < 0.01, respectively). Seven (18%) morbidities occurred in the control vs six (15%) in the study arm. CONCLUSIONS: Patients treated with a cyclo-oxygenase 2-specific inhibitor have a shorter recovery time when compared with patients on a standard postoperative PCA morphine-only regimen after colorectal resection.

Ng et al 2003

Analgesic effects of parecoxib following total abdominal hysterectomy.

Ng A, Smith G, Davidson AC.

Br J Anaesth 2003;90(6):746–749.

BACKGROUND: Forty-eight ASA I-II patients undergoing total abdominal hysterectomy (TAH) were studied in a double blind, randomized placebo controlled trial of parecoxib for postoperative analgesia. METHODS: All patients were given propofol 2-4 mg kg(-1) i.v., a non-depolarizing muscle relaxant, morphine 10 mg i.v. and prochlorperazine 12.5 mg i.m. intraoperatively. Their lungs were ventilated with nitrous oxide and isoflurane 1-1.5% in oxygen. Morphine was self-administered for postoperative analgesia via a patient controlled analgesia (PCA) device. Patients were allocated randomly to receive either parecoxib 40 mg i.v. or normal saline on induction of anaesthesia. RESULTS: Twelve patients did not complete the study. Of the remaining 36 patients, there was no significant difference between the treatment groups in age, weight, ASA status, duration of surgery, or intraoperative dose of morphine. However, mean (95% CI) 24 h morphine consumption of 54 (42-65) mg in the parecoxib group was significantly (P=0.04) lower than that of 72 (58-86) mg in the placebo group. Pain intensity scores on sitting up were significantly lower (P=0.02) in the parecoxib group compared with placebo. There was no significant difference between the treatment groups in pain intensity scores at rest and on deep inspiration, or in nausea, total number of vomiting episodes, median number of rescue antiemetic doses, and sedation scores. CONCLUSIONS: Parecoxib 40 mg i.v. may be recommended in patients having TAH as it provides morphine-sparing analgesia.

Chau-in et al 2008

Prevention of post operative pain after abdominal hysterectomy by single dose etoricoxib.

OBJECTIVE: To test whether a reduction in post operative morphine consumption could be achieved by a single-dose of etoricoxib before induction of anesthesia. DESIGN: Randomized, double-blind, placebo-controlled study. MATERIAL AND METHOD: Two hours before surgery, patients undergoing transabdominal hysterectomy (under general anesthesia) were randomized to a single oral dose of 1) etoricoxib 120 mg (n = 17), 2) etoricoxib 180 mg (n = 17), or 3) placebo (n = 15). Intravenous morphine was given for patient-controlled analgesia (PCA) device. Morphine consumption, pain scores both at rest and on coughing, and side-effects were recorded at 1, 2, 4, 8 and 24 h after surgery. Patients' global evaluation of study medication was assessed at the end of the present study. RESULTS: Etoricoxib provided greater clinical benefit than the placebo in terms of mean morphine in milligram at 24 hour consumption (stardard deviation): a) 26.4 mg (SD of 11.2) for etoricoxib 120 mg; b) 27.2 mg (SD of 9.9) for etoricoxib 180 mg; and, c) 36.6 mg (SD of 8.9) for the placebo group. At 8 h post surgery, pain both at rest and on coughing in the active drug groups was significantly less than in the placebo, while pain on coughing was significantly less at 24 h. Patients reported better global satisfaction and less somnolence in the etoricoxib groups. CONCLUSION: Single dose etoricoxib 180 mg given before surgery provides the same analgesic effect as 120 mg for post operative pain after an abdominal hysterectomy.

Celik et al 2003

A comparative study of the effect of rofecoxib (a COX 2 inhibitor) and naproxen sodium on analgesic requirements after abdominal hysterectomy.

Celik JB, Tuncer S, Reisli R, Sarkilar G, Celik C, Akyurek C.

Arch Gynecol Obstet 2003;268(4):297.

This study evaluated the analgesic efficacy of administering preoperatively rofecoxib or naproxen sodium to patients undergoing abdominal hysterectomy. A randomized, double-blinded prospective study was conducted with 60 women undergoing elective abdominal hysterectomy under general anesthesia. Patients were randomly allocated into one of three equally sized groups. Patients in the first group received rofecoxib 50 mg 1 h before operation (group R), patient in the second group received naproxen sodium 550 mg 1 h before surgery (group N) and patients in the third group received a placebo tablet in the same time (group P). Total amount of used morphine mixture was higher in placebo group (93+/-6 ml) than in the group R (50+/-4 ml) and group N (64+/-6 ml). There were significant difference for total amount of used morphine mixture between group P and other two groups. There was significant difference in the volumes of morphine mixture used in the first 12 h in group P and other two groups. The occurrence of side effects such as, dyspepsia, epigastric discomfort, heartburn, were similar in group R and group P. However, this side effects were increased in group N. Rofecoxib receiving preoperatively was provided clinical efficacy for postoperative pain control and well tolerated for gastrointestinal side effects comparable with naproxen sodium.

Xu et al 2008

PURPOSE: Flurbiprofen axetil (FA) is a potent non-steroidal anti-inflammatory drug (NSAID). We examined the effects that peri-operative intravenous administration of FA, combined with thoracic epidural anesthesia and postoperative patient-controlled epidural analgesia (PCEA), have on bowel function, postoperative pain, and cytokine release, after open colorectal surgery. METHODS: This was a prospective, randomized, double-blind, placebo-controlled study. Forty patients were randomly assigned to one of two groups (n = 20 in each group). The FA group patients received FA 1 mg.kg(-1) iv, 30 min before and six hours after skin incision; whereas the control group patients received an equal volume of intralipid. Blood cytokine levels were measured before FA administration, at the end of surgery, and six hours and 24 hr postoperatively. All patients received postoperative PCEA for pain control. Analgesic efficacy was evaluated for 72 hr postoperatively using visual analogue scale (VAS) pain scores both at rest and during coughing. Gastrointestinal motility was recorded. Temperature and leukocyte count were measured preoperatively, and 24 hr postoperatively. RESULTS: The times to first bowel movement (87 +/- 23 vs 105 +/- 19 hr, P = 0.008) and first flatus (63 +/- 16 vs 75 +/- 11 hr, P = 0.01) were earlier in the FA group compared to the control group. For the first 24 hr, the pain scores in the FA group were also lower during coughing (P < 0.001 compared to control). The plasma concentrations of interleukin (IL)-6 and IL-8 in the FA group were lower, postoperatively (P < 0.01 and P < 0.05, respectively, compared to control). In contrast, the IL-10 levels were significantly increased at six hours, postoperatively, in the FA group (P = 0.009). The total leukocyte count and the incidence of pyrexia were also lower in patients of the FA group (P = 0.001 and P = 0.006, respectively, compared to control). CONCLUSION: Flurbiprofen axetil may have an anti-inflammatory effect in major abdominal surgery. The combination of perioperative intravenous FA, intraoperative thoracic epidural anesthesia, and postoperative PCEA facilitated recovery of bowel function, enhanced analgesia, and attenuated the cytokine response.

Nakayama et al 2001a

STUDY OBJECTIVE: To evaluate the effects of epidurally administered neostigmine on pain after abdominal hysterectomy. DESIGN: Prospective, randomized, double-blind study. SETTING: Teaching hospital. PATIENTS: 45 ASA physical status I adult patients scheduled for abdominal hysterectomy. INTERVENTIONS: All patients received identical general and epidural anesthesia. At the end of the surgery, they received epidural bupivacaine (10 mg) with either saline (control group, n = 15), 5 micro g/kg (5-micro g group, n = 15), or 10 micro g/kg neostigmine (10-micro g group, n = 15). Postoperatively, 50 mg diclofenac suppository was given for pain relief on patient demand. MEASUREMENTS AND MAIN RESULTS: The time to first diclofenac administration and the number of times diclofenac was required during the first 24 postoperative hours were recorded. Pain was assessed using a 10-cm visual analog pain scale (VAS) at rest at the first diclofenac request, and at 15 and 24 hours after surgery. The time to first diclofenac administration was significantly longer (p < 0.05) in the 10-micro g group (223 +/- 15 min) than in the control (78 +/- 17 min) or 5-micro g groups (88 +/- 18 min). However, epidural neostigmine at both doses did not reduce the number of postoperative diclofenac administrations. There were no differences in VAS among the three groups. CONCLUSIONS: Epidural neostigmine of 10 micro g/kg in bupivacaine provides a longer duration of analgesia than does bupivacaine alone or with 5 micro g/kg of neostigmine after abdominal hysterectomy.

Schulze et al 1997

Effect of prednisolone on the systemic response and wound healing after colonic surgery.

OBJECTIVE: To study the effect of preoperative treatment with a single high-dose glucocorticoid on the systemic and immunologic responses, wound healing, and convalescence after colonic surgery. DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING: Department of surgery in a university hospital. PATIENTS: Thirty patients scheduled for open colonic resection; 6 patients were excluded from the study (N = 24). INTERVENTIONS: Patients were randomized to either of 2 treatment regimens: methylprednisolone sodium succinate 90 minutes before induction of anesthesia and epidural analgesia (group 1, n = 12), or placebo 90 minutes before anesthesia and epidural analgesia (group 2, n = 12). MAIN OUTCOME MEASURES: Assessments of pain, pulmonary function, convalescence, and various injury and wound-healing factors were done several times until 10 days after surgery. RESULTS: Conventional reduction in pulmonary function and mobilization was improved in group 1. Interleukin-6 and C-reactive protein levels increased significantly less in group 1, as delayed-type hypersensitivity was abolished in group 1. Plasma cascade system activations were significantly less pronounced in group 1. Reduction of collagen turnover was observed in group 1, but without detrimental effects on collagen accumulation. CONCLUSION: Treatment with a single high-dose glucocorticoid before colonic surgery may improve postoperative pulmonary function and mobilization and reduce plasma cascade system activations, the inflammatory response, and immunofunction, but without detrimental effects on wound healing.

Nagelschmidt et al 1999

OBJECTIVE: To assess the effect of preoperative high dose methylprednisolone on stress response and outcome. DESIGN: Randomised, placebo-controlled, double-blind study. SETTING: University hospital, Germany. SUBJECTS: 20 patients listed for abdominal surgery of whom 10 had major intra-abdominal interventions and 10 had incisional hernias repaired. INTERVENTIONS: Methylprednisolone 30 mg/kg (100 ml) was given by slow intravenous infusion 90-60 minutes before operation. The control group received the same volume of sodium chloride. MAIN OUTCOME MEASURES: Speed of convalescence, degree of fatigue, amount of pain, consumption of analgesics, breathing capacity, and hospital stay, as well as humoral and cellular mediators of the stress response. RESULTS: Methylprednisolone significantly improved criteria of postoperative recovery, fatigue by 47%, (day 1), convalescence by about 45% (days 1-3), and breathing capacity (FEV1) between 47% and 29% (days 5, 7) (p < 0.05, ANOVA), and led to a significant reduction of median hospital stay of 4.5 days. C-reactive protein concentration was significantly decreased (by 46% on day 3) and T-cell activation was suppressed (day 1). CONCLUSION: Outcome of the patients after conventional abdominal surgery is substantially improved by preoperative high dose methylprednisolone. This effect is more pronounced in patients having major operations.

Krantz et al 1990

[Assessment of early postoperative convalescence by a simple scoring system].

Krantz T, Wolff C, Hjortso NC, Kehlet H.

Ugeskr Laeger 1990;152(16):1168–1170.

Fifty patients in classes 1-2 of the American Society of Anaesthesiologists (ASA) were submitted to major elective abdominal surgery. They were anaesthetised with a balanced technique and were assessed preoperatively and daily until the tenth postoperative day by a simple scoring system based on self-care. The total score fell significantly to a minimum on the first postoperative day and remained significantly decreased but with an increasing tendency until the tenth postoperative day. Patients with wound or respiratory complications had significantly lower scores than patients without complications on the sixth to ninth days. It is concluded that this simple scoring system is useful for monitoring early postoperative morbidity and it may prove of value in future investigations of surgical therapeutic regimes.

Sauerland et al 2000

Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review.

Sauerland S, Nagelschmidt M, Mallmann P, Neugebauer EA.

Drug Saf 2000;23(5):449–461.

BACKGROUND: A single preoperative high dose of methylprednisolone (15 to 30 mg/kg) has been advocated in surgery, because it may inhibit the surgical stress response and thereby improve postoperative outcome and convalescence. However, these potential clinical benefits must be weighed against possible adverse effects. OBJECTIVE: To conduct a risk-benefit analysis using a meta-analysis, to compare complication rates and clinical advantages associated with the use of high dose methylprednisolone in surgical patients. METHODS: Randomised controlled trials of high dose methylprednisolone in elective and trauma surgery were systematically searched for in various literature databases. Outcome data on adverse effects, postoperative pain and hospital stay were extracted and statistically pooled in fixed-effects meta-analyses. RESULTS: We located 51 studies in elective cardiac and noncardiac surgery, as well as traumatology. Pooled data failed to show any significant increase in complication rates. In patients treated with corticosteroids, nonsignificantly more gastrointestinal bleeding and wound complications were observed; the 95% confidence interval boundaries of the numbers-needed-to-harm were 59 and 38, respectively. The only significant finding was a reduction of pulmonary complications (risk difference -3.5%; 95% confidence interval -1.0 to -6.1), mainly in trauma patients. CONCLUSION: For patients undergoing surgical procedures, a perioperative single-shot administration of high dose methylprednisolone is not associated with a significant increase in the incidence of adverse effects. In patients with multiple fractures, limited evidence suggests promising benefits of glucocorticoids on pulmonary complications.

OBJECTIVE: To characterize the beneficial effects of perioperative systemic lidocaine on length of hospital stay, gastrointestinal motility, and the inflammatory response after colorectal surgery. SUMMARY BACKGROUND DATA: Surgery-induced stimulation of the inflammatory response plays a major role in the development of several postoperative disorders. Local anesthetics possess anti-inflammatory activity and are thought to positively affect patients' outcome after surgery. This double-blinded, randomized, and placebo-controlled trial aimed to evaluate beneficial effects of systemic lidocaine and to provide insights into underlying mechanisms. METHODS: Sixty patients undergoing colorectal surgery, not willing or unable to receive an epidural catheter, were randomly assigned to lidocaine or placebo treatment. Before induction of general anesthesia, an intravenous lidocaine bolus (1.5 mg/kg) was administered followed by a continuous lidocaine infusion (2 mg/min) until 4 hours postoperatively. Length of hospital stay, gastrointestinal motility, and pain scores were recorded and plasma levels or expression of pro- and anti-inflammatory mediators determined. RESULTS: Lidocaine significantly accelerated return of bowel function and shortened length of hospital stay by one day. No difference could be observed in daily pain ratings. Elevated plasma levels of IL-6, IL-8, complement C3a, and IL-1ra as well as expression of CD11b, L- and P-selectin, and platelet-leukocyte aggregates were significantly attenuated by systemic lidocaine. CONCLUSIONS: Perioperative intravenous lidocaine not only improved gastrointestinal motility but also shortened length of hospital stay significantly. Anti-inflammatory activity modulating the surgery-induced stress response may be one potential mechanism. Systemic lidocaine may thus provide a convenient and inexpensive approach to improve outcome for patients not suitable for epidural anesthesia.

Kuo et al 2006

Comparison of the effects of thoracic epidural analgesia and i.v. infusion with lidocaine on cytokine response, postoperative pain and bowel function in patients undergoing colonic surgery.

Kuo CP, Jao SW, Chen KM, Wong CS, Yeh CC, Sheen MJ, Wu CT.

Br J Anaesth 2006;97(5):640-646.

BACKGROUND: Both thoracic epidural analgesia (TEA) and i.v. lidocaine were able to decrease postoperative pain and duration of ileus. We compared TEA and i.v. lidocaine (IV) regarding their effects on cytokines, pain and bowel function after colonic surgery. METHODS: Sixty patients were randomly allocated to one of the three groups. TEA group had lidocaine 2 mg kg(-1) followed by 3 mg kg(-1) h(-1) epidurally and an equal volume of i.v. normal saline. The IV group received the same amount of lidocaine i.v. and normal saline epidurally. The control group received normal saline via both routes. These regimens were started 30 min before surgery and were continued throughout. Blood cytokines were measured at scheduled times within 72 h. RESULTS: Both TEA and IV groups had better pain relief. The total consumptions using patient-controlled epidural analgesia were 81.6 (6.5), 55.0 (5.3) and 45.6 (3.9) ml (P<0.01) and the times of flatus passage were 50.2 (4.9), 60.2 (5.8) and 71.7 (4.7) h (P<0.01) in the TEA, IV and control groups, respectively. The TEA group exhibited the best postoperative pain relief and the least cytokine surge. The IV group experienced better pain relief and less cytokine release than the control group. CONCLUSIONS: The TEA lidocaine had better pain relief, lower opioid consumption, earlier return of bowel function and lesser production of cytokines than IV lidocaine during 72 h after colonic surgery; IV group was better than the control group.

We tested the ability of two L-type calcium channel blockers (nifedipine and nimodipine) and the N-methyl D-aspartate natural antagonist magnesium to decrease morphine requirements and pain in the postoperative period in 92 patients undergoing elective colorectal surgery. In a randomized, double-blinded study, patients were assigned to one of four groups. The control group received placebo. The nifedipine group received 60 mg of oral nifedipine. The magnesium group received an initial dose of 30 mg/kg followed by 10 mg x kg(-1) x h(-1) of magnesium sulfate over 20 h. The nimodipine group received 30 microg x kg(-1) x h(-1) of nimodipine over 20 h. Postoperative morphine consumption was assessed for 48 h. Pain at rest and pain on movement were assessed up to the fifth day postsurgery. There were no differences among groups in postoperative morphine consumption at 12 and 24 h. The nifedipine group consumed more morphine than the control and nimodipine groups during 24-48 h. Pain at rest scores were higher at 16 and 24 h in the nifedipine group than in the other three groups. Pain on movement scores were lower at 72 h in the nimodipine group than in the control and nifedipine groups. In conclusion, the perioperative application of oral nifedipine, IV nimodipine, or IV magnesium sulfate failed to decrease postoperative morphine requirements after colorectal surgery. Implications: The increase of intracellular calcium plays a key role in spinal transmission of pain and in the establishment of central sensitization. We examined the effects of nifedipine, nimodipine, and magnesium sulfate in postoperative analgesia after colorectal surgery. We found no differences in morphine consumption with the administration of each drug alone.

Colonic surgery is associated with severe postoperative pain and postoperative ileus, which contribute to delayed hospital discharge. In previous studies, we demonstrated that IM dextromethorphan (DM) provided preemptive analgesia and improved postoperative pain. The benefit of thoracic epidural anesthesia (TEA) and postoperative epidural analgesia on postoperative pain was well demonstrated. The goal of this study was to investigate the effect of preincisional IM DM combined with intraoperative TEA and postoperative patient-controlled epidural analgesia (PCEA) on pain and bowel function after colonic surgery. Patients were randomized into 3 equal groups to receive: 1) chlorpheniramine maleate (CPM) 20 mg and general anesthesia (CPM-GA); 2) CPM 20 mg and GA combined with TEA (CPM-TEA); or 3) DM 40 mg (containing 20 mg of CPM) and GA combined with TEA (DM-TEA). The CPM, DM, and TEA with lidocaine were administered after GA induction via an IM injection and 30 min before the skin incision. All patients received postoperative PCEA for pain control. Analgesic effects were evaluated for 72 h after surgery using visual analog scale pain scores at rest and moving, time to first PCEA request for pain relief, total PCEA consumption, and the time to first passage of flatus. Statistically significant improvement of postoperative pain and bowel function was observed in the following order: DM-TEA > CPM-TEA > CPM-GA. Compared with the CPM-TEA group, the DM-TEA group averaged 1.6 points lower on first-hour pain scores, 40 min longer to first PCEA request, 15.8 mL less PCEA drug over 72 h, and 14.7 h earlier bowel function (all P < 0.01). We conclude that the combination of preincisional DM (40 mg IM), intraoperative TEA, and postoperative PCEA enhances analgesia and facilitates recovery of bowel function, suggesting possible synergistic interaction with local anesthetics and opioids.

Fassoulaki et al 1995

Preemptive opioid analgesia does not influence pain after abdominal hysterectomy.

Fassoulaki A, Sarantopoulos C, Zotou M, Papoulia D.

Can J Anaesth 1995;42(2):109–113.

Opioid administration before surgical stimulus may reduce or prevent subsequent pain. We studied the effect of timing of opioid administration on the pain-related behaviour after abdominal hysterectomy. Eighty-five patients scheduled for abdominal hysterectomy were blindly randomized to receive fentanyl 10 micrograms.kg-1 before induction of anaesthesia (FA), after peritoneal incision (FB) or after removal of the uterus (FC), or sufentanil 1 micrograms.kg-1 before induction of anaesthesia (SA) or after peritoneal incision (SB) respectively. All patients received a standard postoperative analgesic regimen. The time from skin closure to the first analgesic request was recorded. Pain was assessed using the VAS and a verbal rating score (VSR 1 = no pain to 6 = intolerable pain) every 30 min until patients asked for the first analgesic, and 24 hr postoperatively. The times from skin closure to the first analgesic request did not differ among the five groups. The VAS scores using the two-way ANOVA with repeated measurements differed among the five groups (F = 4.046, df = 4, 213, P < 0.005). The VAS scores with one-way ANOVA differed among the five groups 30 min postoperatively (F = 4.542, df = 4, 58, P < 0.003), being higher in the FA (6.5 +/- 1.8) and SA (5.9 +/- 2.1) groups than in the FC (3.2 +/- 2.5) group, and at 120 min postoperatively (F = 3.217, df = 4, 18, P < 0.05), being higher in the FA than in the FB group (6.1 +/- 1.5 and 2.6 +/- 1.9 respectively).(Abstract truncated at 250 words)

Kilickan et al 2001

The effect of preemptive intravenous morphine on postoperative analgesia and surgical stress response.

Kilickan L, Toker K.

Panminerva Med 2001;43(3):171–175.

BACKGROUND: Although initial studies of preemptive analgesia showed that preoperative blockade with local anaesthetics or preoperative administration of systemic opioids was more effective in reducing postoperative pain than control conditions involving no treatment, the result of subsequent investigations comparing the effects of preoperative treatment with the same treatment initiated after surgery have produced inconsistent RESULTS. The reasons for the lack of consistency are not clear. Studies about the relationship of preemptive analgesia and both analgesic consumption and surgical stress response are limited. The purpose of this study was to evaluate the effect of preemptive intravenous morphine on both postoperative analgesic consumption and surgical stress response. METHODS: Sixty patients, ASA I or II, aged 20-60, undergoing total abdominal hysterectomy plus bilateral salpingo-oopherectomy and double-blinded were randomly assigned to three groups of 20 patients. Group I (n=20) received 0.15 mg/kg of morphine following induction and placebo saline during peritoneal closure. Group II (n=20) received placebo saline following induction and 0.15 mg/kg of morphine during peritoneal closure. Group III (n=20) received placebo saline both during induction and peritoneal closure. Blood cortisol, glucose levels and leukocyte count were measured in the pre and postoperative period. RESULTS: Postoperative total morphine consumption was significantly lower in group I compared with group III (p<0.001). In all groups, plasma cortisol levels increased significantly within 4 hours of surgery as compared to pre-op values (p<0.001). Plasma glucose also increased to a significantly higher level in all groups in the postoperative 30 min and 8 hours than in the pre-op values (p<0.001). Postoperative leukocytosis was observed in all groups and the leukocyte count was significantly greater during postoperative 24 h than pre-op values (p<0.001). CONCLUSIONS: Preemptive morphine 0.15 mg/kg intravenous has decreased total morphine consumption but has failed to suppress the surgical stress response.

Wordliczek et al 2002

Influence of pre- or intraoperational use of tramadol (preemptive or preventive analgesia) on tramadol requirement in the early postoperative period.

The aim of this study was to assess the influence of iv tramadol on opioid requirement in the early postoperative period. The subjects were 90 patients scheduled for colon surgery (hemicolectomy) who received general anesthesia using the (N2O/O2) isoflurane technique. Thirty patients (group I) were administered 100 mg of tramadol iv before induction of general anesthesia (preemptive analgesia). Group II (30 patients) was administered 100 mg of tramadol iv immediately after peritoneal closure (preventive analgesia) and control group (30 patients) received 100 mg of tramadol iv immediately after operation. Following the operation, all patients were administered tramadol in the PCA-iv mode in order to treat postoperative pain. In the postoperative period, the following parameters were measured: pain intensity (using VAS), total consumption of tramadol, time until the first PCA activation, and frequency of side effects (drowsiness, nausea, vomiting). In patients of groups I and II who had received preemptive or preventive analgesia, a significantly lower total consumption of tramadol, as compared with control group, was observed in the early postoperative period. However, the time until the first PCA activation was significantly shorter in group I as compared to the other two groups. No significant differences between the groups were found regarding pain intensity and frequency of side effects.

Simpson et al 1993

A pilot study of pain, analgesia use, and pulmonary function after colectomy with or without a preoperative bolus of epidural morphine.

Simpson T, Wahl G, DeTraglia M, Speck E, Taylor D.

Heart Lung 1993;22(4):316–327.

OBJECTIVE: To determine whether patients who received a preoperative bolus of epidural morphine plus postoperative parenteral analgesia had less pain and better pulmonary function over the first 2 days after a colectomy than patients who received postoperative parenteral analgesia alone. DESIGN: Repeated measures, quasi-experimental, random assignment. SETTING: Northeastern general hospital. SUBJECTS: Thirteen patients were randomized to receive parenteral with (n = 6) or without (n = 7) epidural analgesia. OUTCOME MEASURES: Indicators of pain (intensity of pain and pain-related distress, intensity of words used to describe pain, intramuscular-equivalent amount of morphine administered, duration from start of surgery to first request for analgesia) and pulmonary function (forced expiratory volume in one second FEV1], forced vital capacity [FVC], inspiratory capacity [IC], peripheral oxygen saturation [SaO2] values). MEASUREMENT: Indicators of pain and pulmonary function were obtained the day before surgery, approximately 6 hours after surgery, and the first two mornings after surgery. RESULTS: Six hours after surgery, patients in the epidural group had less pain (p = 0.0177) and related distress (p = 0.0303) and greater FVC (p = 0.0303) and FEV1 (p = 0.0025) than patients in the no-epidural group. On the first postoperative morning, patients in the epidural group had less distress related to pain (p = 0.0350) but similar respiratory rates and spirometry values. Inspiratory capacity was not statistically different but was always larger in the epidural group. Of patients who breathed room air, SaO2 was higher in the epidural group over the first two postoperative days (p = 0.0286 each occasion). Patients in the epidural group received their first on-demand analgesic an average of 30 hours after the start of surgery compared with 6 hours for patients in the no-epidural group (p = 0.0022). There were no significant differences in the total number of words used to describe the type of pain, and both groups described the pain with fewer words than expected on the first and second mornings after surgery. CONCLUSIONS: Results should be confirmed through study of a larger sample with the hypothesis that pain relief, selected aspects of pulmonary function, and peripheral oxygenation may be superior for patients who receive a preoperative bolus of epidural analgesia for abdominal surgery.

The postoperative period is associated with an increased production of cytokines, which augment pain sensitivity. We investigated the hypothesis that epidural clonidine premedication and postoperative patient-controlled epidural analgesia (PCEA) including clonidine would decrease the release of proinflammatory (interleukin (IL)-6, IL-1beta, IL-8, and tumor necrosis factor (TNF)-alpha) and antiinflammatory (IL-1 receptor antagonist (RA)) cytokines in patients who underwent elective colorectal surgery and that they would provide better postoperative analgesia. Forty patients were randomly assigned to 1 of 2 groups of 20 each: the control group received normal saline 10 mL, whereas the clonidine group received epidural clonidine 150 microg diluted with 9 mL of normal saline 30 min before surgery. Venous blood samples for cytokine levels were obtained before induction, at the end of surgery, and after surgery at 12 and 24 h. After surgery, the clonidine group patients received PCEA with morphine (0.1 mg/mL) and clonidine (1.5 microg/mL) in 0.2% ropivacaine 100 mL, whereas control group patients received only PCEA morphine and ropivacaine. Patients in the clonidine group exhibited longer PCEA trigger times, lower pain scores at rest and while coughing, less morphine consumption, and a faster return of bowel function throughout the 72-h postoperative observation period, compared with patients in the control group. For patients in the clonidine group, production of IL-1RA, IL-6, and IL-8 was significantly less increased at the end of the surgical procedure and at 12 and 24 h after surgery. However, the concentrations of IL-1beta and TNF-alpha were not significantly increased.

Dahl et al 1992

Influence of timing on the effect of continuous extradural analgesia with bupivacaine and morphine after major abdominal surgery.

Dahl JB, Hansen BL, Hjortso NC, Erichsen CJ, Moiniche S, Kehlet H.

Br J Anaesth 1992;69(1):4–8.

We have studied the effect of continuous extradural analgesia with bupivacaine and morphine, initiated before or after colonic surgery, in a double-blind, randomized study. Thirty-two patients were allocated randomly to receive an identical extradural block initiated 40 min before surgical incision (n = 16) or at closure of the surgical wound (n = 16). The extradural regimen consisted of a bolus of 7 ml of plain bupivacaine 7.5 mg ml-1 plus morphine 2 mg and continuous extradural infusion of a mixture of bupivacaine 7.5 mg ml-1 plus morphine 0.05 mg ml-1, 4 ml h-1 for 2 h, followed by a continuous extradural infusion of a mixture of bupivacaine 2.5 mg ml-1 plus morphine 0.05 mg ml-1, 4 ml h-1, continued for 72 h after operation. In addition, all patients received similar general anaesthesia. There was no significant difference in request for additional morphine and no significant differences between the groups in pain scores (visual analogue scale or verbal) during rest or ambulation at any time of measurement. These results do not suggest that timing of analgesia with a conventional extradural regimen is of major clinical importance in patients undergoing colonic surgery.

Goyagi et al 1999

This study was designed to evaluate the effects of oral clonidine premedication on postoperative analgesia by epidural morphine in a prospective, randomized, double-blinded design. Sixty consenting patients, scheduled for total abdominal hysterectomy, were randomly assigned to one of three groups (n = 20 each); the clonidine-morphine group received oral clonidine 5 microg/kg 90 min before arriving in the operating room and epidural morphine 2 mg before induction of general anesthesia, the clonidine-placebo group received oral clonidine 5 microg/kg and no epidural morphine, and the placebo-morphine group received no clonidine and epidural morphine 2 mg. An epidural catheter was placed at the L1-2 or L2-3 interspace, and 1.5% lidocaine was used for surgical anesthesia in all patients. General anesthesia was then induced with propofol, and maintained with a continuous infusion of propofol and 67% nitrous oxide in oxygen during surgery. Four patients were subsequently withdrawn from the study. After surgery, patient-controlled analgesia using IV morphine was used to assess analgesic requirement. Morphine consumptions determined every 6 h after surgery in the clonidine-morphine and placebo-morphine groups were significantly less than the clonidine-placebo group until 12 h after surgery, whereas those of the clonidine-morphine group were significantly less than the placebo-morphine group from 13 to 42 h after surgery. Visual analog (pain) scale (VAS) scores in the clonidine-morphine group were significantly lower than the placebo-morphine group at 48 h at rest, and at 1, 24, 36, and 48 h with movement. Similarly, VAS scores in the clonidine-morphine group were significantly lower than the clonidine-placebo group at 1 and 6 h both at rest and with movement, whereas VAS scores in the clonidine-placebo group were significantly lower than the placebo-morphine group at 24, 36, and 48 h at rest and with movement. The incidence of nausea and pruritus was similar between groups. We conclude that the combination of oral clonidine and epidural morphine produces more potent and longer lasting postoperative analgesia than either drug alone without increasing the incidence of adverse effects after major gynecologic surgeries. IMPLICATIONS: A small dose of epidural morphine is often used for postoperative analgesia. We found that oral clonidine premedication 5 microg/kg improves the analgesic efficacy of epidural morphine without increasing the incidence of adverse side effects.

Abdel-Ghaffar et al 1998

PURPOSE: To study the analgesic effect of epidural ketamine on postoperative pain and epidural PCA consumption after total abdominal hysterectomy. METHODS: Sixty-one ASA I–II patients, 34–60 yr were randomly assigned into three groups. Epidural catheters were inserted before induction of anaesthesia. Patients in group I and II received 30 mg ketamine epidurally before induction of anaesthesia or 20 min after skin incision: group III received placebo. Postoperatively, on first analgesia request, sedation score, Visual Analogue Scale (VAS), Prince Henry Score (PHS) and Bromage motor weakness score were taken and followed by an epidural bolus of 9 ml bupivacaine 0.25% + 50 µg fentanyl. Analgesia was maintained by PCA with a mixture of bupivacaine 0.1% + fentanyl 0.001% epidurally. Measurements were repeated at 1, 2, 4, 8, 12 and 24 hr. RESULTS: First analgesia request was 17 +/- 6.8 min in the control group compared with 31.4 +/- 23.8 and 44 +/- 23.1 min for groups I and II respectively. The differences between group III and group I (P < 0.05) and between group III and group II (P < 0.01) were statistically significant. Twenty four hour PCA consumption was 101.2 +/- 47.2, 87 +/- 27 and 162 +/- 38 ml for groups I, II and III respectively. The differences between group III and group I and that between group III and group II were statistically significant (P < 0.001). CONCLUSION: Epidural ketamine 30 mg reduces post hysterectomy pain as evidenced by prolongation of time to first analgesia request and reduction in postoperative epidural PCA consumption. This effect is manifest whether ketamine is given before induction or 20 min after skin incision.

In a double-blind, randomized study, we investigated 40 patients undergoing abdominal hysterectomy; patients received 0.5% plain bupivacaine 20 ml via a low thoracic extradural catheter and a diclofenac suppository (100 mg), either 30 min before incision (group 1) or 30 min after incision (group 2). All patients received a standard general anaesthetic and no opioid was used before or during operation. Postoperative analgesic requirements were measured using a patient-controlled analgesia (PCA) system. Pain was assessed using a visual analogue scale (VAS) and a verbal pain score (VPS) on movement up to 48 h after operation. There was no significant difference in the time to first request for morphine but consumption of morphine was significantly greater in group 1 at all times except 24 h. There were no significant differences in VAS and VPS pain scores, although both scores were consistently higher in group 1. Patient satisfaction with the quality of analgesia, at 24 h, demonstrated no significant difference between the two groups. The combination of extradural block and diclofenac suppository given before operation did not appear to produce a clinically effective pre-emptive analgesic effect.

Schulze et al 1992

Effect of combined prednisolone, epidural analgesia, and indomethacin on the systemic response after colonic surgery.

Twenty patients undergoing colonic resection were randomized to either conventional postoperative pain treatment with morphine chloride and acetaminophen (group 1, n = 9) or methylprednisolone sodium succinate 90 minutes before surgery plus intraoperative neural blockade, with a postoperative analgesic regimen with combined bupivacaine hydrochloride-morphine and indomethacin sodium for systemic effect (group 2, n = 11). Assessments of pain, pulmonary function, convalescence, and various injury factors were done several times until 8 days after surgery. Postoperative pain and hyperthermic response were eliminated in group 2. Conventional reduction in pulmonary function measures was improved in group 2, and fatigue and mobility were less pronounced. Prostaglandin E2, interleukin 6, and C-reactive protein levels increased in both groups, but significantly less in group 2. These results suggest that a combined neural and humoral blockade may more effectively inhibit the global stress response to elective surgery than previously observed with neural blockade with or without indomethacin.

BACKGROUND: The aim of the study was to evaluate whether perioperative epidural analgesia had any effect on the duration of postoperative ileus after laparoscopic sigmoid resection. METHODS: Twenty patients were randomized to surgery either with (group 1; n = 10) or without (group 2; n = 10) thoracic epidural analgesia. The major endpoint of the study was the time to the first postoperative bowel movement. Secondary endpoints were the interval until oral feeding was tolerated, incidence of postoperative vomiting, postoperative analgesic consumption use of patient-controlled analgesia (PCA) until the fourth day after operation, subjective pain perception and the incidence of epidural-related side-effects. RESULTS: Age, sex and American Society of Anesthesiologists classification were similar in the two groups. The first bowel movement was documented after a median of 54 (95% confidence interval 32–127) h in group 1 and 77 (31–99) h in group 2 (p = 0.8). Oral feeding without additional parenteral therapy was tolerated after 48 (40–64) h in group 1 and after 56 (48-64) h in group 2 (p = 0.6). Postoperative vomiting occurred in two patients from each group. During epidural therapy the use of PCA was lower in group 1 (0.30 (0.19–0.96) mg morphine per kg) than in group 2 (0.56 (0.37–0. 80) mg/kg) (p < 0.05). Postoperative pain perception during rest and while coughing was similar in both groups. Three patients experienced reversible side-effects of epidural therapy (motor deficit, two patients; bladder dysfunction, one). CONCLUSION: Perioperative thoracic epidural analgesia did not have a clinically relevant effect on the duration of postoperative ileus after laparoscopic sigmoid resection.